Case SeriesPneumothorax in Mechanically Ventilated Patients with COVID-19 Infection

Raziye Ecem Akdogan,1 Turab Mohammed ,1 Asma Syeda,1 Nasheena Jiwa,2

Omar Ibrahim,2 and Rahul Mutneja 3

1Department of Internal Medicine, University of Connecticut, Farmington, Connecticut, USA2Department of Pulmonary and Critical Care Medicine, University of Connecticut, Farmington, Connecticut, USA3Department of Pulmonary and Critical Care Medicine, Saint Francis Hospital and Medical Center, Hartford, Connecticut, USA

Correspondence should be addressed to Rahul Mutneja; rahul.mutneja@trinityhealthofne.org

Received 3 November 2020; Revised 6 December 2020; Accepted 5 January 2021; Published 11 January 2021

Academic Editor: Mehmet Doganay

Copyright © 2021 Raziye Ecem Akdogan et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

Data on patient-related factors associated with pneumothorax among critically ill patients with COVID-19 pneumonia is limited.Reports of spontaneous pneumothorax in patients with coronavirus disease 2019 (COVID-19) suggest that the COVID-19infection could itself cause pneumothorax in addition to the ventilator-induced trauma among mechanically ventilated patients.Here, we report a case series of five mechanically ventilated patients with COVID-19 infection who developed pneumothorax.Consecutive cases of intubated patients in the intensive care unit with the diagnosis of COVID-19 pneumonia andpneumothorax were included. Data on their demographics, preexisting risk factors, laboratory workup, imaging findings,treatment, and survival were collected retrospectively between March and July 2020. Four out of five patients (4/5; 80%) had abilateral pneumothorax, while one had a unilateral pneumothorax. Of the four patients with bilateral pneumothorax, three (3/4;75%) had secondary bacterial pneumonia, two had pneumomediastinum and massive subcutaneous emphysema, and one ofthese two had an additional pneumoperitoneum. A surgical chest tube or pigtail catheter was placed for the management ofpneumothorax. Three out of five patients with pneumothorax died (3/5; 60%), and all of them had bilateral involvement. Thedata from these cases suggest that pneumothorax is a potentially fatal complication of COVID-19 infection. Large prospectivestudies are needed to study the incidence of pneumothorax and its sequelae in patients with COVID-19 infection.

1. Introduction

Pneumothorax, defined by the presence of air in the pleuralcavity with or without collapse of the lung, is often a life-threatening complication and a medical emergency [1]. Itcan be classified into spontaneous, iatrogenic, or traumaticpneumothorax based on the etiology [2]. Iatrogenic pneumo-thorax occurs from a complication of a diagnostic or thera-peutic intervention such as transthoracic-needle aspiration,placement of a central venous catheter, thoracentesis, lung,and or pleural biopsy, or barotrauma [3, 4]. During the coro-navirus disease 2019 (COVID-19) pandemic, an increase inpneumothorax incidence, especially among mechanicallyventilated patients with COVID-19 infection, has beenobserved. The mechanical ventilation has deleterious effects

on the lung, and pneumothorax is a known complication oflung ventilation [5]. Ventilation-related pneumothorax hasbeen more commonly reported in the pediatric populationdue to immature lung mechanics [6, 7]. Although spontane-ous pneumothorax has been reported with infections, includ-ing COVID-19 [8, 9], the probability of pneumothoraxincreases from the combination of parenchymal injury fromunderlying infection and inflammatory response with addi-tional positive pressure ventilation. A study on 202 patientsfrom Wuhan, 12 (5.9%) patients developed pneumothoraxon mechanical ventilation [10]. Here, we present a case seriesof five patients with pneumothorax among 150 patients ofCOVID-19 pneumonia admitted to the intensive care unitat a tertiary care center.

Information is summarized in Table 1.

HindawiCase Reports in Critical CareVolume 2021, Article ID 6657533, 8 pageshttps://doi.org/10.1155/2021/6657533

Table1:Patient

characteristics.

Case

Age

Sex

Race

Com

orbidities

Smoking

history

Dayson

intubation

during

the

event

Mod

eof

ventilation

Ventilatorsettings

atthetimeof

theevent

(FiO2%

)(PEEP)

Superimpo

sed

pneumon

iaSeverity

ofpn

eumotho

rax

Managem

entOutcome

162

MAfrican

American

Obesity,

bullous

lung

disease,CAD,

OSA

Non

smoker

49PC-A

C65%,10

Staphylococcus

aureus

pneumon

iaBilateralp

neum

otho

races

Chesttube

drainage

Deceased

260

MCaucasian

Obesity,H

TN,

OSA

Non

smoker

14PRVC-A

C80%,8

Escherichiacoli

pneumon

ia

Right-sided

tension

pneumotho

rax,subsequent

left-sided

mod

erate

pneumotho

rax

Chesttube

drainage

Deceased

358

MCaucasian

Obesity,H

TN,

MVP

Form

ersm

oker

31VC-A

C50%,8

N/A

Right-sided

pneumotho

rax,

left-sided

tension

pneumotho

rax

Chesttube

drainage

Deceased

464

MCaucasian

CAD

Form

ersm

oker

25PC-A

C40%,6

Staphylococcus

aureus

andgram

-negative

pneumon

ia

Bilateralp

neum

otho

races

Chesttube

drainage

Survived

569

FHispanic

Obesity,

asthma

Non

smoker

12VC-A

C50%,8

N/A

Right-sided

pneumotho

rax

14Fr

pigtail

catheter

Survived

CAD:coron

aryartery

disease;FiO2:

fraction

ofinspired

oxygen;H

TN:h

ypertension;

MVP:m

itralvalveprolapse;P

C-A

C:p

ressurecontrol-assistcontrol;PEEP:p

ositiveendexpiratory

pressure;P

RVC-A

C:

pressure

regulatedvolumecontrol-assistcontrol;OSA

:obstructive

sleepapnea;VC-A

C:volum

econtrol-assistcontrol.

2 Case Reports in Critical Care

2. Case Description

2.1. Case 1. A 62-year-old morbidly obese African Americanmale patient with a past medical history of coronary arterydisease (CAD) and obstructive sleep apnea (OSA) presentedwith seven days of progressive dyspnea. On presentation, hewas hypoxic, and blood work was notable for leukocytosis.Chest X-ray (CXR) showed patchy bilateral opacities, andthe COVID-19 polymerase chain reaction (PCR) test waspositive. He was admitted for acute hypoxic respiratory fail-ure secondary to COVID-19 pneumonia, which was furthercomplicated with superimposed Staphylococcus aureus bacte-rial pneumonia. The patient’s respiratory status deteriorated,and he was subsequently intubated on pressure control set-tings. He had a prolonged hospital course, and his treatmentregimen included vasopressors, steroids, broad-spectrumantibiotic therapy, and convalescent plasma therapy withoutmuch clinical improvement. The following CXR demon-strated extensive subcutaneous emphysema.

A computed tomography (CT) scan of the chest, abdo-men, and pelvis revealed moderate bilateral pneumothoraceswith pneumomediastinum and a large pneumoperitoneum(Figures 1(a) and 1(b)). Ventilation settings around the timeof pneumothorax were pressure control/assist control mode(PC/AC), respiratory rate (RR) of 30 breaths per minute,inspiratory pressure (IP) 34mmH20, inspiratory time (IT)0.8 sec, positive end-expiratory pressure (PEEP) 10 cmH20,and the fraction of inspired oxygen (FiO2) 65%. Tube thora-

costomy with a 28 French (Fr) surgical catheter was per-formed (Figure 1(c)). He had been intubated for a total of49 days owing to the family values. However, given thepatient’s poor overall prognosis, his care was transitioned tocomfort measures only.

2.2. Case 2. A 60-year-old morbidly obese, Caucasian malepatient with a past medical history of hypertension, pre-sented with fever and nonproductive cough for three days.He was admitted for acute hypoxic respiratory failure sec-ondary to COVID-19 pneumonia. A chest CT scan demon-strated extensive bilateral ground-glass opacities. Thepatient was intubated on pressure control settings due to adecline in respiratory status. His hospital course was furthercomplicated by Escherichia coli pneumonia. He was treatedwith Remdesivir, broad-spectrum antibiotics, steroids, vaso-pressors, and convalescent plasma. The patient initiallydeveloped a small right-sided apical pneumothorax duringthe hospital course, which resolved spontaneously withoutintervention. However, a repeat CXR obtained a few dayslater revealed a large right-sided tension pneumothorax(Figure 2(a)), requiring immediate 24 Fr surgical chest tubeplacement (Figure 2(b)), further complicated by an air leak.At that time, the ventilation settings were ventilatory modepressure regulated volume control (PRVC/AC), RR 26, tidalvolume (TV) 650ml, IP 28 cmH20, IT 1.1 second, PEEP8 cmH20, and FiO2 80%. Subsequently, the patient alsodeveloped a left-sided pneumothorax requiring a 28 Fr

(a) (b)

(c)

Figure 1: (a) CT of the chest showing moderate-sized left pneumothorax (red arrow), pneumomediastinum (green arrow), and extensivesubcutaneous emphysema of the chest wall (yellow arrow). (b) Abdominal CT with large pneumoperitoneum (brown arrow) andsubcutaneous emphysema of the abdominal wall (yellow arrow). (c) CXR demonstrating right-sided chest tube and subcutaneousemphysema of chest wall.

3Case Reports in Critical Care

surgical chest tube. Due to worsening bilateral pneu-mothoraces and increasing FiO2 requirements without clini-cal improvement, the patient’s care was transitioned tocomfort measures only.

2.3. Case 3. A 58-year-old Caucasian overweight male, aformer smoker and hypertensive with no underlying lungdisease, was admitted with acute hypoxic respiratory failure.Over the next few days, he deteriorated and was intubatedfor persistent hypoxemia. He received azithromycin andhydroxychloroquine, two doses of tocilizumab, and convales-cent plasma therapy. He had been on pressure control (PC),and on day 16 of intubation, he underwent a bronchoscopyfor evaluation of hemoptysis, which demonstrated bloodybronchoalveolar lavage. The next day he developed bilateralpneumothorax. He was placed on a 14 Fr pigtail catheterfor left-sided pneumothorax and 28 Fr surgical chest tubefor the right-sided tension pneumothorax. His ventilationsettings were PC/AC, RR 22, PEEP of 8 cm H20, and FiO250%.

He underwent tracheostomy placement on day 21. Sub-sequently, the chest tubes were removed, and he was transi-tioned to a trach mask. The patient was doing well andundergoing chest physical therapy when he became acutelyshort of breath and hypotensive.

A chest CT scan revealed a new right-sided pneumotho-rax, left-sided tension pneumothorax, pneumomediastinum,and subcutaneous emphysema of the chest wall (Figure 3).Emergent surgical chest tubes, 28 Fr on the right and 32 onthe left, were placed again, and the patient was reintubated.He subsequently developed empyema and sepsis and eventu-ally passed away.

2.4. Case 4. A 64-year-old morbidly obese Caucasian malewith a past medical history of coronary artery disease pre-sented with five days of fever and progressive shortness ofbreath. He had a 10-pack year smoking history; however,he had quit 40 years ago. He was hypoxic on admission andrequired high flow nasal cannula. He was subsequently intu-bated due to worsening hypoxia and was placed on pressurecontrol settings. He developed superimposed Staphylococcusaureus and gram-negative bacterial pneumonia requiringmultiple rounds of broad-spectrum antibiotics. He underwent

tracheostomy and percutaneous endoscopic gastrostomy(PEG) tube placement. Later in his hospital course, his oxygensaturation dropped with a cuff leak from the tracheostomytube, which prompted reintubation. The following CXR

Figure 3: CT scan of the chest showing left-sided tensionpneumothorax (red arrow), right-sided pneumothorax,pneumomediastinum (green arrow), and extensive subcutaneousemphysema of the chest wall (yellow arrow) with an indwellingright-sided chest tube.

Figure 4: CXR showing persistent right-sided pneumothorax,pneumomediastinum, and the supraclavicular diffusesubcutaneous emphysema with a bilateral chest tube.

(a) (b)

Figure 2: (a) CXR showing a large right-sided pneumothorax. (b) CXR showing resolution of the pneumothorax post chest tube placement.

4 Case Reports in Critical Care

revealed bilateral pneumothoraces, and at that time, theventilator settings were volume control/assist control mode(VC/AC), RR 20, TV 500ml, PEEP 6 cmH2O, and FiO240%. He required bilateral tube thoracostomy with 28 Frsurgical chest tubes (Figure 4). He had a prolonged hospitalcourse and was eventually discharged upon clinicalimprovement.

2.5. Case 5. A 69-year-old Hispanic morbidly obese female,nonsmoker with pertinent history of moderate persistentasthma, obstructive sleep apnea on continuous positive pres-sure ventilation was admitted with fever and cough and latertested positive for COVID-19. She was intubated for hypox-emia. She received azithromycin, hydroxychloroquine, andtocilizumab. On day 12, the patient suddenly started to desa-turate. Her ventilatory settings were VC/AC mode, RR 35,TV 400ml, PEEP 8 cmH20, and FiO2 of 50%. She was draw-

ing tidal volumes of 220ml and breathing at a rate of 35/min.CXR revealed the right-sided pneumothorax requiringimmediate 14 Fr pigtail catheter placement. Subsequently,her volumes and oxygenation improved. After three days,she was extubated, but her hospital course was complicatedby bilateral pulmonary emboli requiring continuous intrave-nous heparin infusion despite thromboprophylaxis. Unfortu-nately, she developed right sided hemothorax (Figure 5(a))from the therapeutic anticoagulation and had a 28 Fr surgicalchest tube and drainage (Figure 5(b)). The patient’s chesttube was removed six days later, and she was discharged afew days later for short term rehab.

3. Discussion

Pneumothorax has been reported with many infections likeInfluenza [11], Herpes simplex virus [12], and Pneumocystis

(a)

(b)

Figure 5: (a) Chest CT showing large right-sided hemothorax as a complication of therapeutic anticoagulation for pulmonary embolism. (b)CXR showing reexpanded lung on the right after placement of the chest tube.

5Case Reports in Critical Care

pneumonia [13]. Although acute respiratory distress syn-drome (ARDS) is the primary cause of mortality in COVID-19 infection, early diagnosis and treatment of serious compli-cations such as pneumothorax [14, 15], pneumomediastinum[16, 17], or pulmonary embolism [18] also carry utmostimportance.

Incidence and an average number of days for the devel-opment of iatrogenic pneumothorax in mechanically venti-lated ARDS patients are unclear. However, studies suggestthat the incidence has reduced since the advent of the protec-tive lung ventilation strategy [6]. Older studies from the pre-protective lung strategy era reported that the pneumothoraxmostly developed within the first couple of weeks of mechan-ical ventilation, and the risk decreased with time [19, 20]. Inlight of the current practice, pneumothorax incidencedepends on the severity and duration of ARDS and ventilatormode.

Spontaneous pneumothorax has been reported in multi-ple case reports in COVID-19 infection [9, 21–24]. Anec-dotal evidence suggests that the natural course of theCOVID-19 infection predisposes to pneumothorax develop-ment [25, 26]. Even though the mechanism of the injury isnot fully understood, there are several proposed theories.Like other respiratory infections related to alveolar injury,the damage from the COVID-19 infection and resultantrupture of the alveolar wall causes cystic formations withinthe lungs. The ischemic parenchymal damage, injury fromthe activation of the inflammatory processes, and fibroblastactivation all precipitate fibro-myxoid exudates, promotingpulmonary cystic lesions [25, 27]. Some researchers havehypothesized that increased respiratory effort and persistentcough generate severe intrapulmonary strain, which resultsin the rupture of alveolar cysts [28]. Among patients requir-ing long-term respiratory support like in COVID-19 pneu-monia, mechanical ventilation creates a persistent alveolarpressure gradient that could accelerate the cyst ruptureleading to air escape of out of pulmonary tissue [29]. Thisair could traverse through visceral pleura and form sub-pleural air cysts [30]. Pneumothorax often occurs throughthe rupture of these subpleural air cysts. Occasionally,escaped air dissects along the perivascular and peribronchialvascular sheath into the mediastinum, retroperitoneum, andsubcutaneous tissue leading to pneumomediastinum, pneu-moperitoneum, or subcutaneous emphysema, respectively.Pneumothorax can also occur when mediastinal pleura rup-ture after the occurrence of pneumomediastinum [31, 32].Furthermore, the probability of such devastating complica-tions is exacerbated by the high-pressure mechanical ventila-tion, especially for a prolonged duration, as it triggers theformation and progression of new alveolar cysts that eventu-ally rupture, resulting in the spread of air into various inter-connected body spaces.

Clinically, pneumothorax can range from an asymptom-atic to a life-threatening condition, and the managementstrategy depends on the degree of clinical compromise. Smallpneumothorax in clinically stable patients can be managedby observation; however, larger pneumothorax with hemo-dynamic instability mandating active intervention to preventcatastrophic sequelae [31, 32]. Blood patch may not be useful

since the patients have spontaneous coagulation abnormali-ties and or are on anticoagulation. If air leak is persistentdespite drainage, thoracoscopy with resection of blebs andpleural scratch could be a treatment choice [33]. Potentialstrategies that need to be investigated include identifyingindividuals at high risk for pneumothorax like those withunderlying parenchymal lung disease and developing anewer lung ventilation strategy pertinent to patients withCOVID-19 infection to avoid volume or pressure-inducedalveolar injury and subsequent complications. Several casereports have shown that barotrauma-related pneumothoraxand pneumomediastinum occur in mechanically ventilatedpatients with COVID-19 infection. Among these withpneumothorax, tube thoracostomy, and drainage has shownsatisfactory outcomes [33]. In a retrospective study byMcGuinness et al., barotrauma-related complications werereported to occur in 24% of patients. This study also notedthat barotrauma was an independent risk factor for deathin COVID-19 infection. [34].

A recent multicenter case series from hospitals across theUnited Kingdom also noted pneumothorax and pneumome-diastinum in patients with COVID-19 infection. They evalu-ated whether pneumothorax is an independent marker ofpoor prognosis in patients with this complication. This studyalso included nonintubated patients, suggesting that patientswith no preexisting lung disease and who have not requiredpositive pressure ventilation were also susceptible to pneu-mothorax; therefore, barotrauma alone cannot explain thisassociation [35]. In the above case series, only two amongthe sixty patients with pneumothorax developed bilateralpneumothoraces sequentially. Unlike in our case series, fourout of five had bilateral pneumothoraces, and three of themdied despite bilateral chest tube placements. Though a smallsample size, our case series suggests that pneumothoraxcould be a risk factor for recurrent pneumothoraces. In thecase series by Martinelli, it was also observed that 28-daysurvival was not different among patients with COVID-19infection even in those with pneumothorax, suggesting thatpneumothorax was not associated with poor prognosis inCOVID-19 pneumonia. The lung damage caused by super-imposed bacterial infections likely predisposes the lung tomultiple pneumothoraces, as seen in 3 out of 5 of ourpatients. The difference in the results observed in our caseseries could be explained by the small sample size, comorbid-ities of the patients such as four out of five patients in ourstudy were morbidly obese, and three out of five had theunderlying pulmonary disease at the time of admission.

The major limitations of our study include small samplesize and the retrospective nature; therefore, we are unableto determine the incidence of pneumothorax and evaluatethe differences in mortality rate and overall survival forpatients with COVID-19 infection with or without baro-trauma. Besides, an observational case series like ours cannotprove the causality of pneumothorax due to COVID-19infection.

Our study results can be used to fuel future studies toassess whether pneumothorax can be used as a prognosticfactor, whether it is an independent marker of mortality,especially among the critically ill patients with COVID-19

6 Case Reports in Critical Care

infection. Furthermore, managing patients with pneumotho-rax with ARDS on mechanical ventilation can be challengingif they are refractory to chest tube drainage with persistent airleak. Our study can be further developed to evaluate patientswith a persistent air leak and whether the possible need forsurgical intervention for pneumothoraces would provide amortality benefit.

4. Conclusion

Pneumothorax can be a life-threatening complication ofsevere lung injury from COVID-19 pneumonia and the highventilator setting required to manage it. We believe second-ary infections also may play a role by causing further lungdamage. Immediate recognition of this complication is ofutmost importance, as one episode of pneumothorax couldbe a risk factor for recurrent pneumothorax. Though the trueincidence of pneumothorax in mechanically ventilatedpatients with COVID-19 infection is unknown, our caseseries suggests that it is an appreciable number and shouldbe kept in mind if there is a sudden change in the clinical sta-tus of an intubated patient. Continued use of already provenlung-protective ventilation strategies and interventions toprevent secondary bacterial infections would also help.

Data Availability

The data used to support the findings of this study areavailable from the corresponding author upon request.

Consent

No written consent has been obtained from the patients asthere is no patient identifiable data included in this caseseries.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

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8 Case Reports in Critical Care